Design and Development of drug delivery systems for solubility enhancement of Nimodipine

Abstract

The prime objective of pursuing this research work was to develop a solid oral dosage form of nimodipine employing different solubility enhancement techniques i.e. self microemulsifying drug delivery system (SMEDDS), liquisolid compacts and inclusion complexation. All three formulations were developed and evaluated for in vitro and in vivo parameters. In vitro drug release was observed in both compendial and biorelevent media to predict drug release pattern. In vivo pharmacokinetic and pharmacodynamic studies were performed to measure AUC, Cmax, Tmax and systolic mean blood pressure respectively. Stability studies were conducted at long term and accelerated conditions. SMEDDS was developed using Capryol 90 (Oil), Cremophore EL (surfactant), PEG 400 (co-solvent) and the resulting liquid SMEDDS was adsorbed on Syloid XDP 3050 to transform it into solid SMEDDS. Liquisolid compacts system was developed by dissolving the drug in Tween 20 (non-volatile vehicle), adsorbed on Avicel PH 102 (carrier material) and then coated using Syloid XDP 3050 to obtain free flowing, compressible powder. Inclusion complex was prepared in which inclusion of nimodipine (hydrophobic molecule) into hydrophobic cavity of hydroxylpropylbetacyclodextrin was generated and the resulting mixture was adsorbed onto Avicel PH 102 to make powder freely flowable and compressible. Solid SMEDDS did not show promising drug release compared to liquisolid compacts and inclusion complexation. But Solid SMEDDS showed the highest AUC, Cmax and lowest Tmax compared to both formulations and an immediate fall in systolic blood pressure was observed rat after administration of solid SMEDDS. Thus it was considered as better approach over other two for nimodipine.